Mycobacterium abscessus
Mechanisms of ResistanceThe TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessusMycobacterium abscessus is a human pathogen responsible for severe respiratory infections, particularly in patients with underlying lung disorders. Notorious for being highly resistant to most antimicrobials, new therapeutic approaches are needed to successfully treat M. abscessus-infected patients...
SusceptibilityNew β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of β-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical IsolatesThe new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the in vitro activity of β-lactam antibiotics against bacteria of the Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activities of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and...
Mechanisms of Action: Physiological EffectsVerapamil Improves the Activity of Bedaquiline against Mycobacterium abscessus In Vitro and in MacrophagesDue to intrinsic multidrug resistance, pulmonary infections with Mycobacterium abscessus are extremely difficult to treat. Previously, we demonstrated that bedaquiline is highly effective against Mycobacterium abscessus both in vitro and in vivo. Here, we report that verapamil...
SusceptibilityAuranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in Mycobacterium abscessusNontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for Mycobacterium abscessus. New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for...
SusceptibilitySynergistic Efficacy of β-Lactam Combinations against Mycobacterium abscessus Pulmonary Infection in MiceMycobacterium abscessus is an emerging pathogen capable of causing invasive pulmonary infections in patients with chronic lung diseases. These infections are difficult to treat, necessitating prolonged multidrug therapy, which is further complicated by extensive intrinsic and acquired resistance exhibited by clinical...
SusceptibilityIn Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical IsolatesWe evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii. However, bedaquiline showed low MIC values for the major pathogenic NTM, including...
Editor's Pick Mechanisms of Action: Physiological EffectsBedaquiline Eliminates Bactericidal Activity of β-Lactams against Mycobacterium abscessusThe β-lactams imipenem and cefoxitin are used for the treatment of Mycobacterium abscessus lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of M. abscessus with the antimycobacterial ATP...
PharmacologyPreclinical Pharmacokinetic and Pharmacodynamic Data To Support Cefoxitin Nebulization for the Treatment of Mycobacterium abscessusMycobacterium abscessus is responsible for difficult-to-treat chronic pulmonary infections in humans. Current regimens, including parenteral administrations of cefoxitin (FOX) in combination with amikacin and clarithromycin, raise compliance problems and are frequently associated with high failure and development of resistance.
Biologic Response ModifiersMycobacterium abscessus Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum MediumMycobacterium abscessus is a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due to M. abscessus’s high intrinsic antibiotic resistance.
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